Treatment with magnetic fluids

ABSTRACT

A magnetic fluid is provided comprising a block copolymer stabilizer, magnetic particles and a fluid poly(alkylsiloxane) medium. The stabilizer comprises of cyano containing polysiloxane block which chelates magnetic metal particles, and at least one end block comprising polysiloxane blocks which are compatible with the medium.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is based on U.S. Provisional Application Ser.No. 60/046,171, filed May 12, 1997, incorporated herein by reference infull.

FIELD OF THE INVENTION

[0002] This invention relates to methods for treating disorders using amagnetic fluid. More specifically, the invention relates to a method fortreating a detached retina using a magnetic fluid in combination with amagnetized sclera buckle, and to methods for directing delivery of acompound by using a magnetic fluid carrier.

BACKGROUND OF THE INVENTION

[0003] The mammalian eye comprises two chambers. The anterior chamber isbounded by the cornea and lens, and contains the aqueous humor. Thevolume behind the lens contains the vitreous humor, with the retinaattached to the back wall of the eye. The retinal layer is not firmlyattached to the eye, and can become detached, resulting in eventualdeath of the retina and loss of vision. The retina may detach along anedge, e.g. as the result of trauma, or as the result of a tear allowingfluid to leak underneath the retina and separate the retina from theunderlying choroid. Retinal detachment can be treated by means of ascleral buckle, a silicone band that encircles the eye and compressesthe wall of the eye inward against the retina. Alternatively, thevitreous humor may be replaced in whole or in part with a tamponade, aheavy liquid or gas intended to flatten the retina against the choroid.

[0004] Currently used internal tamponades (SF₆, C₃F₈, silicone oil)float up, leaving the inferior retina unprotected, or sink down(fluorosilicone), leaving the superior retina unprotected. Currenttamponades also fill the vitreous cavity, decreasing vision, and contactanterior chamber structures, causing cataract and glaucoma.

SUMMARY OF THE INVENTION

[0005] A new method for treating retinal detachment is provided,combining use of a magnetic fluid tamponade with a magnetized scleralbuckle, which effects tamponade of the retinal margin withoutinterfering with vision.

[0006] One aspect of the invention is a method for treating retinaldetachment, by administering to the vitreal chamber a sufficient amountof a magnetic fluid, and applying a magnetized sclera buckle to the eye.

[0007] Another aspect of the invention is a magnetic fluid tamponadesuitable for use in the eye.

[0008] Another aspect of the invention is a magnetized scleral bucklesuitable for use in the method of the invention.

[0009] Another aspect of the invention is a method for delivering acompound to a relatively inaccessible location, by combining thecompound with a magnetic fluid, administering the resulting compositionat an accessible location, and directing the composition to therelatively inaccessible location by magnetic attraction.

[0010] One object of the invention is to provide a method and apparatusfor effecting a retinal tamponade along the periphery of the retina,without contacting the lens or anterior chamber structures, orobstructing the vitreous cavity.

[0011] Another object of the invention is to provide a means forshielding the macula from radiation retinopathy.

[0012] Another object of the invention is to provide for local deliveryof intraocular chemotherapeutic or radiotherapeutic agents.

[0013] Another object of the invention is to provide a stable magneticsilicone fluid.

[0014] Another object of the invention is to provide a magnetizedscleral buckle.

SUMMARY OF THE DRAWINGS

[0015]FIG. 1 is a cross-sectional view of an eye having a magnetizedscleral buckle and a magnetic fluid tamponade.

[0016]FIG. 2 is a cross-sectional view of an eye having a magnetizedexoplant and magnetic fluid.

DETAILED DESCRIPTION

[0017] Definitions

[0018] The term “magnetic fluid” as used herein refers to abiocompatible liquid having magnetic particles dispersed throughout.Magnetic fluids can be manipulated using magnetic fields.

[0019] The term “biocompatible” refers to materials which do not causeundue inflammation or injury when in extended contact with livingtissue.

[0020] The term “effective amount” as used herein refers to an amount ofmagnetic fluid sufficient to hold a detached retina in place. Ingeneral, an effective amount will be the amount necessary to form a ringaround the inside of the vitreal chamber having a thickness of at leastabout 1 mm, and a width of about 1 to about 7 mm.

[0021] The term “cross-linkable polymer” refers to a flexible plasticpolymer which can be rendered rigid by addition of a crosslinking agentor catalyst.

[0022] The term “magnetic particles” refers to metallic particles thatare attracted to magnetic fields.

[0023] The term “relatively inaccessible location” refers to a sitewithin the body that is difficult to directly access through standardsurgical techniques without undue or unacceptable damage to surroundtissue. Examples of relatively inaccessible locations includeintracranial regions and intraocular sites, where surgical access cancarry the risk of brain damage or loss of vision.

[0024] The term “exoplant” or “localized scleral exoplant” refers to agenerally flat patch that is sutured or adhered to the outer surface ofthe eye.

[0025] General Method

[0026] Magnetic fluids useful in the invention are preferablybiocompatible. Thus, the magnetic fluid preferably comprises a non-toxicpolymer carrier, such as a fluid dimethyl-siloxane, hydrogel or thelike. The fluid may further comprise surfactants and/or dispersingagents to stabilize the combination of polymer and magnetic particles. Apresently preferred stabilizer is a block polymer having a central blockof poly(3-cyanopropyl)-methylsiloxane flanked by blocks ofpolydimethylsiloxane. Block copolymers are often more efficient thanhomopolymers as dispersion stabilizers. The stabilizer comprises“anchor” blocks which strongly absorb onto the magnetic particlesurface, and “tail” blocks which protrude into the medium. Triblockcopolymers are preferred having a poly(3-cyanopropyl)methylsiloxane(PCPMS) “anchor” block flanked by two polydimethyl-siloxane (PDMS)“tail” blocks. Approximately equal volumes of stabilizer and magneticparticles are used, and typically together constitute about 2% to about50% of the volume of the magnetic fluid, preferably about 5% to about30%, most preferably about 10% by volume. The ratio of stabilizer tomagnetic particles is from about 1:10 to about 10:1, preferably fromabout 3:5 to about 5:3, most preferably about 1:1 by volume. Theremainder of the magnetic fluid comprises the non-toxic biocompatiblecarrier, and optionally other stabilizers and preservatives.

[0027] The block copolymer stabilizers are made according to the methoddescribed in Li et al., “Polydimethylsiloxane-b-Poly(3-cyanopropyl)methylsiloxane-b-Polydimethyl-siloxane Triblock Suspension Stabilizers”,Polymer Preprints, August, 1996, which is incorporated by referenceherein in its entirety.

[0028] The magnetic particles are any ferromagnetic element or compound,including without limitation Fe, Ni, Co, Fe₂O₃, Neodymium, Samarium, andthe like, and are preferably about 2-10 nm in maximum diameter. Themedium is a polyalkylsiloxane, such as polydimethylsiloxane.

[0029] The amount of stabilizer used will depend upon the concentrationof magnetic particles required to hold the tamponade in place with amagnetized scleral buckle of given magnetic strength. This may bedetermined empirically by those of ordinary skill.

[0030] The stabilizer, comprising an anchor block which binds to metaland two tail blocks which are compatible with silicone fluid, is used tosuspend magnetic particles in silicone fluid. The anchor blocks ofpoly(3-cyanopropyl)methylsiloxane (PCPMS) with reactive cyano end groupsare prepared using an anionic redistribution reaction of cyclicmonomers. Li et al., supra. The stabilizer having a PCPMS anchor blockflanked by two polydimethylsiloxane (PDMS) tail blocks are formed usinglithium silanolate terminated PCPMS to polymerize hexamethyltrisiloxane.Li et al., supra.

[0031] γ-Fe₂O₃ powder (or other magnetic particles) is dispersed insilicone monomer containing minor amounts of the triblock stabilizerswith ultrasonification.

[0032] While not being bound to a theory, it is believed that thestabilizer produces a stable colloidal suspension because:

[0033] 1. The block copolymers are strongly absorbed onto the metalsurface via the central cyano-containing PCPMS “anchor” block.

[0034] 2. The “tail” blocks of PDMS extend into the PDMS medium. Inclose proximity, the mutual repulsion of these tails causes them toextend as far as possible into the medium.

[0035] 3. The particles tend not to coagulate because approach of theparticle-stabilizer complexes causes an unfavored decrease in entropy.

[0036] 4. Also, coagulation of the particles requires desorption orlateral surface movement of the stabilizers which is an unfavored energyrequirement.

[0037] The scleral buckle comprises a flexible biocompatible material,suitable for application to the sclera. The buckle is preferably aflexible silicone band, dimensioned to fit snugly around the eye andgently compress the eye so that the inner surface of the vitreal chamberis urged into contact with the periphery of the retina. The buckle ispreferably fabricated by combining medical grade siloxane with magneticparticles (as described above for the magnetic fluid) prior tocross-linking or curing. Buckles can be provided in the form of stripsor rings, generally as a relatively flat band. Rings are provided in aplurality of different diameters, to accommodate eyes of differentsizes. Strips can be provided in any length, and cut to fit at the timeof application, followed by connecting the ends of the strip. Strips andrings are preferably cast in their final form. Scleral exoplants orpatches are formed in the same way, and can optionally be provided withpositioning straps.

[0038]FIG. 1 is a cross-sectional view of an eye 101 having cornea 102,lens 103, choroid 104, retina 105, vitreal chamber 107, magnetic scleralbuckle 106 and magnetic fluid 110 of the invention. In the practice ofthe invention, a subject is generally first diagnosed as having retinaldetachment. The method of the invention is particularly suited fortreating holes along the periphery of the retina 109. The eye is firstsubjected to a partial or total vitrectomy (removal of part or all ofthe vitreous humor) by surgical methods. The magnetic fluid is applied,for example using a syringe, and the magnetic scleral buckle 106 ispositioned immobilized in place, generally by suture or adhesive. Thescleral buckle attracts the magnetic fluid 110 to an annular positioninside the eye, closest to the retinal periphery 109.

[0039] Detachments in other regions of the retina can also be treated,by positioning the scleral buckle over the detached region, or byapplying a magnetized exoplant. FIG. 2 is a cross-sectional view of aneye 200 having a magnetic fluid tamponade 202 held in place by amagnetized exoplant 201. The exoplant 201 can be fixed in place usingadhesive, sutures, and/or positioning bands 203. The localized exoplantis also suitable for treating intraocular tumors, when used incombination with a magnetic fluid 202 containing a chemotherapeutic orradiotherapeutic agent. Further, one can employ an exoplant to shieldthe macula from radiation damage during cancer treatment by applying anexoplant to the sclera such that magnetic fluid injected into thevitreous chamber covers the macula. The magnetic fluid partially shieldsthe macula from the effects of radiation, which may otherwise lead toradiation retinopathy. The exoplant and fluid can be removed at theconclusion of treatment.

[0040] An encircling magnetized scleral buckle and magnetic fluidproduces a 360 degree ring of magnetic fluid in apposition to theretinal periphery. Furthermore, the central vitreous cavity is free ofmagnetic fluid, and there is no contact between the magnetic fluid andthe lens, anterior chamber structures, and macula.

EXAMPLE

[0041] Neodymium/iron particles are dispersed in polysiloxanes withacetoxy functional groups which condense in the presence of atmosphericmoisture at low temperature to yield crosslinked polydimethylsiloxaneelastomers. These are molded in an appropriate configuration for sclerabuckling elements, having about 10% by volume magnetic particles.

What is claimed is:
 1. A method for treating retinal detachment in aneye, comprising: inserting an effective amount of magnetic fluid intothe vitreal chamber of said eye; and applying a magnetized scleralbuckle to said eye.
 2. The method of claim 1, wherein a portion of thevitreous humor is removed prior to inserting said magnetic fluid.
 3. Themethod of claim 2, wherein the entire vitreous humor is removed.
 4. Themethod of claim 1, wherein said scleral buckle is sutured in place. 5.The method of claim 1, wherein said magnetic fluid comprises across-linkable polymer.
 6. The method of claim 5, wherein said methodfurther comprises crosslinking said magnetic fluid after applying saidscleral buckle.
 7. A scleral buckle for treating a detached retina in aneye comprising: a flexible biocompatible band dimensioned to fit aroundsaid eye; wherein said buckle comprises magnetic particles.
 8. Thebuckle of claim 7, wherein said magnetic particles have a diameter ofabout 2 to about 10 nm.
 9. The buckle of claim 8, wherein said particlescomprise iron, nickel, or neodynium.
 10. The buckle of claim 7, whereinsaid buckle exerts pressure sufficient to slightly deform the eye whenapplied.
 11. A method for delivering a compound to a relativelyinaccessible internal location in a subject, the method comprising:administering at an accessible site in said subject a magnetic fluidcomprising a biocompatible carrier, magnetic particles, and a compound;and transporting said magnetic fluid to said relatively inaccessiblelocation by magnetic attraction.
 12. The method of claim 11, whereinsaid relatively inaccessible location is intracranial.
 13. The method ofclaim 11, wherein said relatively inaccessible location is intraocular.14. The method of claim 11, wherein said relatively inaccessiblelocation is intra-abdominal.
 15. The method of claim 11, wherein saidcompound is selected from the group consisting of chemotherapeutics,radiotherapeutics, and antimicrobials.
 16. A method for protecting themacula from radiation during radiation treatment of an eye, comprising:eye, comprising: (a) applying a magnetic exoplant to the scleraimmediately outside the macular region of the eye; and region of theeye; and (b) injecting a magnetic fluid into the vitreal chamber of theeye, in an amount sufficient to cover the macula.
 17. The method ofclaim 16, further comprising: (c) exposing the eye to a therapeuticamount of radiation.